Abstract

Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis.

We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to monitor changes in bone microarchitecture and strength at the distal radius and tibia associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Despite treatment-associated declines in total and cortical BMD, trabecular thinning and reduced trabecular bone volume, bone strength did not change significantly from baseline.
Teriparatide is an established anabolic therapy for osteoporosis; however, treatment effects at the distal radius are unclear. Therefore, we aimed to monitor changes in bone microarchitecture and estimated strength at the distal radius and tibia in osteoporotic postmenopausal women.
We used high-resolution peripheral quantitative computed tomography (Scanco Medical, Switzerland) to perform a standard three-dimensional morphological analysis of the distal radius and tibia in 11 osteoporotic postmenopausal women (mean age, 68.7 ± 12.7 years) at baseline, 6, 12, and 18 months after initiation of 20 μg/day of teriparatide. Ten of the women received bisphosphonate therapy prior to starting on teriparatide. In addition to the standard analysis, we quantified cortical bone mineral density (BMD), porosity, and thickness using an automated segmentation procedure and estimated bone strength (ultimate stress) using finite element analysis.
After 18 months, we observed a decrease in total BMD (p = 0.03) at the distal radius and a decrease in cortical BMD at the distal radius (p = 0.05) and tibia (p = 0.01). The declines in cortical BMD were associated with trends for increased cortical porosity at both sites. At the distal radius, 18 months of teriparatide treatment was also associated with trabecular thinning (p = 0.009) and reduced trabecular bone volume ratio (p = 0.08). We observed similar trends at the distal tibia. Despite these changes in bone quality, bone strength was maintained over the 18-month follow-up.
The observed changes in cortical bone structure are consistent with the effects of parathyroid hormone on intracortical bone remodeling. Controlled trials involving larger sample sizes are required to confirm the effects of teriparatide therapy on trabecular and cortical microarchitecture in the peripheral skeleton.

Macdonald HM, Nishiyama KK, Hanley DA, Boyd SK
Osteoporos Int Jan 2011
PMID: 20458576 | Full Text

Although our sample size was small, our results are consistent with previous reports of declines in cortical BMD at the radius [8, 9, 18] and at the femoral neck [6] with teriparatide therapy. The decrease in cortical BMD in the present study was coupled with increased cortical porosity at both sites; however, cortical porosity was only statistically different from baseline at the distal tibia after 12 months. Despite a more porous cortex, FE analysis indicated that bone strength did not appear to be compro- mised with teriparatide treatment. This finding supports observations from animal models in which treatment with PTH activated intracortical remodeling and lead to in- creased intracortical porosity [19, 20], but did not compro- mise bone strength [20]. This was likely due to localization of the porosity near the endocortical surface where its influence on bone’s mechanical properties is minimal [20], although this spatial distribution needs to be confirmed in future HR-pQCT studies. In the present study, a slightly thicker cortical shell and enlarged cortical area may also have offset the higher cortical porosity at the distal tibia. Similar changes in cortical bone geometry were observed in rabbits [19] and monkeys [20] treated with PTH and were attributed to increased bone formation on the endocortical surface. In addition, postmenopausal women treated with teriparatide for a median of 18 months had significantly larger cortical area at the distal radius compared with untreated women as measured with pQCT, but no pretreatment com- parison was obtained [18]. Whether PTH has an anabolic effect on the periosteal surface remains unclear [19, 20]….

We acknowledge limitations of our study including the small sample size and the fact that all but one of the women had received prior therapy with bisphosphonates. The degree to which prior bisphosphonate therapy blunts the bone response to teriparatide remains unclear, as in some instances, it does not appear to do so [4, 23]. Since distal radius fractures are recognized indicators of osteoporosis [24], there is an obvious need for larger clinical trials that employ HR-pQCT to monitor and compare the treatment- related effects of teriparatide on bone microarchitecture and strength in treatment-naïve subjects and subjects with a history of bisphosphonate therapy.